Georgina Xanthou and her colleagues recently published a study in Allergy

Studies by Xanthou Georgina and colleagues have identified a novel role for autophagy in suppressing NLRP3-driven inflammasome responses and linked airway inflammation in severe asthma. Theofani et. al. discovered an enhancement of NLRP3 inflammasome responses and mTORC1 signaling in circulating monocytes from patients with severe treatment-resistant asthma, concomitant with deficient autophagy activation that correlated with clinical parameters of disease severity. Mechanistic studies revealed defective autophagy induction, along with reduced signaling through the autophagy-related transcription factor, TFEB, as key underlying mechanisms for the exaggerated NLRP3-driven inflammatory responses. In vivo studies in Nlrp3 deficient mice with severe asthma confirmed the clinical observations. Importantly, the authors showed that in vivo activation of the autophagy inducer, TFEB, through trehalose administration or myeloid cell-specific TFEB overexpression, suppressed NLRP3 signaling, restrained pulmonary inflammation and attenuated asthma features. Collectively, these studies uncovered a crucial role for TFEB-mediated reprogramming of monocyte inflammatory responses, raising the prospect that this pathway can be therapeutically harnessed for the management of SA.

pubmed

TFEB signaling attenuates NLRP3-driven inflammatory responses in severe asthma
Theofani E, Semitekolou M, Samitas K, Mais A, Galani IE, Triantafyllia V, Lama J, Morianos I, Stavropoulos A, Jeong SJ, Andreakos E, Razani B, Rovina N, Xanthou G. Allergy. 2022 Jan 17. doi: 10.1111/all.15221.